title: Extensive evaluations of the cytotoxic effects of gold nanoparticles.
abstract: BACKGROUND
  Many in vitro studies have revealed that the interference of dye molecules in traditional nanoparticle cytotoxicity assays results in controversial conclusions. The aim of this study is to establish an extensive and systematic method for evaluating biological effects of gold nanoparticles in mammalian cell lines.
  
  
  METHODS
  We establish the cell-impedance measurement system, a label-free, real-time cell monitoring platform that measures electrical impedance, displaying results as cell index values, in a variety of mammalian cell lines. Cytotoxic effects of gold nanoparticles are also evaluated with traditional in vitro assays.
  
  
  RESULTS
  Among the six cell lines, gold nanoparticles induce a dose-dependent suppression of cell growth with different levels of severity and the suppressive effect of gold nanoparticles was indirectly associated with their sizes and cellular uptake. Mechanistic studies revealed that the action of gold nanoparticles is mediated by apoptosis induction or cell cycle delay, depending on cell type and cellular context. Although redox signaling is often linked to the toxicity of nanoparticles, in this study, we found that gold nanoparticle-mediated reactive oxygen species generation was not sustained to notably modulate proteins involved in antioxidative defense system.
  
  
  CONCLUSIONS
  The cell-impedance measurement system, a dye-free, real-time screening platform, provides a reliable analysis for monitoring gold nanoparticle cytotoxicity in a variety of mammalian cell lines. Furthermore, gold nanoparticles induce cellular signaling and several sets of gene expression to modulate cellular physical processes.
  
  
  CONCLUSIONS
  The systematic approach, such as cell-impedance measurement, analyzing the toxicology of nanomaterials offers convincing evidence of the cytotoxicity of gold nanomaterials.
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Show-Mei
authors.initials: SM
authors.lastname: Chuang
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Lee
authors.forename: Ruei-Yue
authors.initials: RY
authors.lastname: Liang
authors.forename: Gwo-Dong
authors.initials: GD
authors.lastname: Roam
authors.forename: Zih-Ming
authors.initials: ZM
authors.lastname: Zeng
authors.forename: Hsin-Fang
authors.initials: HF
authors.lastname: Tu
authors.forename: Shi-Kwun
authors.initials: SK
authors.lastname: Wang
authors.forename: Pin Ju
authors.initials: PJ
authors.lastname: Chueh
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D004354:Drug Screening Assays, Antitumor; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000633:toxicity*; D020411:Oligonucleotide Array Sequence Analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D017382:Reactive Oxygen Species; D006046:Gold
keywords: Cell-impedance measurement; Cytotoxicity; DNA microarray; Gold nanoparticle; In vitro assay